KR20000023812A - 단백질 티로신 키나제의 억제제인 비시클릭 헤테로방향족 화합물 - Google Patents
단백질 티로신 키나제의 억제제인 비시클릭 헤테로방향족 화합물 Download PDFInfo
- Publication number
- KR20000023812A KR20000023812A KR1019997000298A KR19997000298A KR20000023812A KR 20000023812 A KR20000023812 A KR 20000023812A KR 1019997000298 A KR1019997000298 A KR 1019997000298A KR 19997000298 A KR19997000298 A KR 19997000298A KR 20000023812 A KR20000023812 A KR 20000023812A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- compound
- benzyl
- pyrido
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- -1 Bicyclic heteroaromatic compounds Chemical class 0.000 title claims abstract description 282
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 232
- 238000000034 method Methods 0.000 claims abstract description 76
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 37
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 27
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 8
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000004429 atom Chemical group 0.000 claims abstract description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 212
- 229910052739 hydrogen Inorganic materials 0.000 claims description 93
- 125000003545 alkoxy group Chemical group 0.000 claims description 85
- 239000001257 hydrogen Substances 0.000 claims description 83
- 125000003282 alkyl amino group Chemical group 0.000 claims description 79
- 229910052757 nitrogen Inorganic materials 0.000 claims description 58
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 41
- 239000012453 solvate Substances 0.000 claims description 40
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
- 239000003153 chemical reaction reagent Substances 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 26
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 26
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 16
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000001041 indolyl group Chemical group 0.000 claims description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 13
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- QNDFCSITSCMNGP-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QNDFCSITSCMNGP-UHFFFAOYSA-N 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 150000003852 triazoles Chemical class 0.000 claims description 11
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 10
- 125000004175 fluorobenzyl group Chemical group 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 8
- 150000004702 methyl esters Chemical class 0.000 claims description 8
- 150000003536 tetrazoles Chemical class 0.000 claims description 8
- DYYZXRCFCVDSKD-UHFFFAOYSA-N N6,N6-dimethyl-N4-[1-(phenylmethyl)-5-indazolyl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 DYYZXRCFCVDSKD-UHFFFAOYSA-N 0.000 claims description 7
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 7
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 6
- BMIOWXJYLRLVHA-UHFFFAOYSA-N 4-n-(1-benzylindazol-5-yl)-6-n-methylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(NC)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 BMIOWXJYLRLVHA-UHFFFAOYSA-N 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- JFXFEXXASOCJBR-UHFFFAOYSA-N 4-n-(1-benzylindazol-5-yl)-6-n-ethyl-6-n-methylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)CC)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 JFXFEXXASOCJBR-UHFFFAOYSA-N 0.000 claims description 5
- RLCKHNKPUUYNQD-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 RLCKHNKPUUYNQD-UHFFFAOYSA-N 0.000 claims description 5
- JCMRKIPIHJRILY-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 JCMRKIPIHJRILY-UHFFFAOYSA-N 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 230000002159 abnormal effect Effects 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- HKNPEKHQRROZPD-UHFFFAOYSA-N 4-n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC(F)=C1 HKNPEKHQRROZPD-UHFFFAOYSA-N 0.000 claims description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004989 dicarbonyl group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- GIZAHSJRRRUFEE-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(1,3-dioxolan-2-yl)furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)C=3OC(=CC=3)C3OCCO3)=CC=C2N1CC1=CC=CC=C1 GIZAHSJRRRUFEE-UHFFFAOYSA-N 0.000 claims description 4
- LTGRUCLMFSREMZ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 LTGRUCLMFSREMZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical group C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 claims description 4
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 229910052721 tungsten Inorganic materials 0.000 claims description 4
- 229910052720 vanadium Inorganic materials 0.000 claims description 4
- 125000004277 1,3-dioxalan-2-yl group Chemical group [H]C1([H])OC([H])(*)OC1([H])[H] 0.000 claims description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 3
- UMFFMOFETJMRSZ-UHFFFAOYSA-N 2-[4-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]piperazin-1-yl]-1-morpholin-4-ylethanone Chemical compound C1COCCN1C(=O)CN(CC1)CCN1C(N=CC1=NC=N2)=CC1=C2NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 UMFFMOFETJMRSZ-UHFFFAOYSA-N 0.000 claims description 3
- XKGUJMPYDBMSDA-UHFFFAOYSA-N 4-n-(1-benzyl-3-methylindazol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C(C)=N2)=CC=C1N2CC1=CC=CC=C1 XKGUJMPYDBMSDA-UHFFFAOYSA-N 0.000 claims description 3
- YZZIGXZRNAEFCP-UHFFFAOYSA-N 4-n-(1-benzylindol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2CC1=CC=CC=C1 YZZIGXZRNAEFCP-UHFFFAOYSA-N 0.000 claims description 3
- RCDUEGIHNAMABT-UHFFFAOYSA-N 4-n-(2-benzyl-3h-benzimidazol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1N2)=CC=C1N=C2CC1=CC=CC=C1 RCDUEGIHNAMABT-UHFFFAOYSA-N 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 3
- 229910052770 Uranium Inorganic materials 0.000 claims description 3
- WWAHWFCQESJGIU-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(4-methylpiperazin-1-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 WWAHWFCQESJGIU-UHFFFAOYSA-N 0.000 claims description 3
- NEHINJYPPQYUQH-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-imidazol-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3C=NC=C3)=CC=C2N1CC1=CC=CC=C1 NEHINJYPPQYUQH-UHFFFAOYSA-N 0.000 claims description 3
- OEYOUMHPXUXUIQ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-piperidin-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3CCCCC3)=CC=C2N1CC1=CC=CC=C1 OEYOUMHPXUXUIQ-UHFFFAOYSA-N 0.000 claims description 3
- WVIYDZAMWSNDDO-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-pyrrolidin-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3CCCC3)=CC=C2N1CC1=CC=CC=C1 WVIYDZAMWSNDDO-UHFFFAOYSA-N 0.000 claims description 3
- COGNCPVOUZUOSK-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC=NC=C4N=CN=3)=CC=C2N1CC1=CC=CC=C1 COGNCPVOUZUOSK-UHFFFAOYSA-N 0.000 claims description 3
- DUNKZQKFWZSBHG-UHFFFAOYSA-N n-(1-benzylindol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=C2)=CC=C1N2CC1=CC=CC=C1 DUNKZQKFWZSBHG-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 3
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
- BIQOFKWYWPJGNB-UHFFFAOYSA-N 4-n-[1-(benzenesulfonyl)indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 BIQOFKWYWPJGNB-UHFFFAOYSA-N 0.000 claims description 2
- HBOLGDVBJIQIQE-UHFFFAOYSA-N 4-n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1F HBOLGDVBJIQIQE-UHFFFAOYSA-N 0.000 claims description 2
- MQNRGKYCHYKEMO-UHFFFAOYSA-N 4-n-[1-[(4-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=C(F)C=C1 MQNRGKYCHYKEMO-UHFFFAOYSA-N 0.000 claims description 2
- OCCGRAZNBVMQAO-UHFFFAOYSA-N 4-n-[3-(benzenesulfonyl)-1h-indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C12)=CC=C1NC=C2S(=O)(=O)C1=CC=CC=C1 OCCGRAZNBVMQAO-UHFFFAOYSA-N 0.000 claims description 2
- VKPHMHJHCQWKKV-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-2-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=N1 VKPHMHJHCQWKKV-UHFFFAOYSA-N 0.000 claims description 2
- USTNKMJFNDVPLS-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-3-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CN=C1 USTNKMJFNDVPLS-UHFFFAOYSA-N 0.000 claims description 2
- 108010077895 Sarcosine Proteins 0.000 claims description 2
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000007942 carboxylates Chemical class 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical group COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 2
- FRHWAVXLZREEEK-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(C)=NN=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 FRHWAVXLZREEEK-UHFFFAOYSA-N 0.000 claims description 2
- QLNPJNIYZWVSMB-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(C)=NN=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=C(F)C=CC=2)N=C2)C2=C1 QLNPJNIYZWVSMB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 229940043230 sarcosine Drugs 0.000 claims description 2
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- 150000003456 sulfonamides Chemical class 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 150000003018 phosphorus compounds Chemical class 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- 150000002390 heteroarenes Chemical class 0.000 abstract description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 165
- 239000000203 mixture Substances 0.000 description 60
- 239000007787 solid Substances 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 18
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 18
- 239000000047 product Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 108060006698 EGF receptor Proteins 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- BQUSMTPKYUILPD-UHFFFAOYSA-N 1-benzylindazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 BQUSMTPKYUILPD-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- QCEPAUUUYZXMGD-UHFFFAOYSA-N 4-chloro-n,n-dimethylpyrido[3,4-d]pyrimidin-6-amine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1Cl QCEPAUUUYZXMGD-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 150000003246 quinazolines Chemical class 0.000 description 5
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 5
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 5
- UYDNPZLYDODKKA-UHFFFAOYSA-N 1-benzylindol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 UYDNPZLYDODKKA-UHFFFAOYSA-N 0.000 description 4
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 4
- CKPNVNAKQGYUSK-UHFFFAOYSA-N 4,6-dichloropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1Cl CKPNVNAKQGYUSK-UHFFFAOYSA-N 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- HDJLSECJEQSPKW-UHFFFAOYSA-N Methyl 2-Furancarboxylate Chemical compound COC(=O)C1=CC=CO1 HDJLSECJEQSPKW-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 101150093908 PDGFRB gene Proteins 0.000 description 4
- 102000001332 SRC Human genes 0.000 description 4
- 108060006706 SRC Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- BTNPJMNKYNWUPD-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC(F)=C1 BTNPJMNKYNWUPD-UHFFFAOYSA-N 0.000 description 3
- MACVPLPBEJHWHK-UHFFFAOYSA-N 1-benzyl-3-methyl-5-nitroindazole Chemical compound C12=CC=C([N+]([O-])=O)C=C2C(C)=NN1CC1=CC=CC=C1 MACVPLPBEJHWHK-UHFFFAOYSA-N 0.000 description 3
- LONPVIGEVNTHTN-UHFFFAOYSA-N 1-benzyl-5-nitroindole Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 LONPVIGEVNTHTN-UHFFFAOYSA-N 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 3
- JQXJBXVWVPVTOO-UHFFFAOYSA-L 4-diphenylphosphanylbutyl(diphenyl)phosphane;palladium(2+);dichloride Chemical compound Cl[Pd]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 JQXJBXVWVPVTOO-UHFFFAOYSA-L 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 101150008206 Cilk1 gene Proteins 0.000 description 3
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 229910052796 boron Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229960005141 piperazine Drugs 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 2
- BHOSCKKNURHTND-UHFFFAOYSA-N 1-(benzenesulfonyl)indol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 BHOSCKKNURHTND-UHFFFAOYSA-N 0.000 description 2
- LXFNLRHJSUSBFL-UHFFFAOYSA-N 1-(pyridin-2-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=N1 LXFNLRHJSUSBFL-UHFFFAOYSA-N 0.000 description 2
- ZSFTXNIYPDDDSG-UHFFFAOYSA-N 1-(pyridin-3-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CN=C1 ZSFTXNIYPDDDSG-UHFFFAOYSA-N 0.000 description 2
- KJRSYMJRLSJMOZ-UHFFFAOYSA-N 1-N,1-N-dimethyl-2H-pyridine-1,4-diamine Chemical compound CN(N1CC=C(C=C1)N)C KJRSYMJRLSJMOZ-UHFFFAOYSA-N 0.000 description 2
- HNAXFSKDGWBXFI-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1F HNAXFSKDGWBXFI-UHFFFAOYSA-N 0.000 description 2
- VHWVWFPJTDRKIK-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=C(F)C=C1 VHWVWFPJTDRKIK-UHFFFAOYSA-N 0.000 description 2
- NCALXEWOPBPBQR-UHFFFAOYSA-N 1-benzyl-3-methylindazol-5-amine Chemical compound C12=CC=C(N)C=C2C(C)=NN1CC1=CC=CC=C1 NCALXEWOPBPBQR-UHFFFAOYSA-N 0.000 description 2
- KACWEIWGSHNESJ-UHFFFAOYSA-N 1-benzyl-5-nitroindazole Chemical compound N1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 KACWEIWGSHNESJ-UHFFFAOYSA-N 0.000 description 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 2
- XZNGFDIIMTUDLO-UHFFFAOYSA-N 2-(4-chloropyrido[3,4-d]pyrimidin-6-yl)-5-methyl-1,3,4-oxadiazole Chemical compound O1C(C)=NN=C1C1=CC2=C(Cl)N=CN=C2C=N1 XZNGFDIIMTUDLO-UHFFFAOYSA-N 0.000 description 2
- SRLUJNCPQPGUKZ-UHFFFAOYSA-N 2-(dimethylamino)-5-(2,2-dimethylpropanoylamino)pyridine-4-carboxylic acid Chemical compound CN(C)C1=CC(C(O)=O)=C(NC(=O)C(C)(C)C)C=N1 SRLUJNCPQPGUKZ-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- MQTBODNTRQAUSK-UHFFFAOYSA-N 2-benzyl-3h-benzimidazol-5-amine Chemical compound N1C2=CC(N)=CC=C2N=C1CC1=CC=CC=C1 MQTBODNTRQAUSK-UHFFFAOYSA-N 0.000 description 2
- UMWIVOZCYNITGG-UHFFFAOYSA-N 2-benzyl-6-nitro-1h-benzimidazole Chemical compound N1C2=CC([N+](=O)[O-])=CC=C2N=C1CC1=CC=CC=C1 UMWIVOZCYNITGG-UHFFFAOYSA-N 0.000 description 2
- AMYYUKGKCJKCBI-UHFFFAOYSA-N 2-methylsulfonylethanamine;hydrochloride Chemical compound Cl.CS(=O)(=O)CCN AMYYUKGKCJKCBI-UHFFFAOYSA-N 0.000 description 2
- RNUNUPZAHSFZPH-UHFFFAOYSA-N 3-(benzenesulfonyl)-1h-indol-6-amine Chemical compound C=1NC2=CC(N)=CC=C2C=1S(=O)(=O)C1=CC=CC=C1 RNUNUPZAHSFZPH-UHFFFAOYSA-N 0.000 description 2
- KCGZHOPKWJEWIO-UHFFFAOYSA-N 4-(furan-2-yl)-1-methyl-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC(C)(CO2)COC12C1=CC=CO1 KCGZHOPKWJEWIO-UHFFFAOYSA-N 0.000 description 2
- UCQOIQWWCPATPS-UHFFFAOYSA-N 4-chloro-6-phenylmethoxypyrido[3,4-d]pyrimidine Chemical compound C1=C2C(Cl)=NC=NC2=CN=C1OCC1=CC=CC=C1 UCQOIQWWCPATPS-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- HGWZRWMSONEISS-UHFFFAOYSA-N 4-n-(3-benzyl-2h-indazol-6-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1NN=2)=CC=C1C=2CC1=CC=CC=C1 HGWZRWMSONEISS-UHFFFAOYSA-N 0.000 description 2
- MXZQLVOKPYMZSH-UHFFFAOYSA-N 4-n-(3-benzylsulfonyl-2h-indazol-6-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1NN=2)=CC=C1C=2S(=O)(=O)CC1=CC=CC=C1 MXZQLVOKPYMZSH-UHFFFAOYSA-N 0.000 description 2
- WDNVTYCNDLLHTL-UHFFFAOYSA-N 4-oxo-1h-pyrido[3,4-d]pyrimidine-6-carbonitrile Chemical compound N1=C(C#N)C=C2C(=O)NC=NC2=C1 WDNVTYCNDLLHTL-UHFFFAOYSA-N 0.000 description 2
- XMOBKRSGYZRORK-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carboxylic acid;hydrochloride Chemical compound Cl.O1C(C(=O)O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 XMOBKRSGYZRORK-UHFFFAOYSA-N 0.000 description 2
- PEXVJBCQKQZYOI-UHFFFAOYSA-N 5-amino-2-(dimethylamino)pyridine-4-carboxylic acid Chemical compound CN(C)C1=CC(C(O)=O)=C(N)C=N1 PEXVJBCQKQZYOI-UHFFFAOYSA-N 0.000 description 2
- VRNHWAZLHPUTSM-UHFFFAOYSA-N 6-(2h-tetrazol-5-yl)-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound C1=C2C(=O)NC=NC2=CN=C1C1=NN=NN1 VRNHWAZLHPUTSM-UHFFFAOYSA-N 0.000 description 2
- IVRTWLXZVOGNQN-UHFFFAOYSA-N 6-(5-methyl-1,3,4-oxadiazol-2-yl)-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound O1C(C)=NN=C1C1=CC(C(NC=N2)=O)=C2C=N1 IVRTWLXZVOGNQN-UHFFFAOYSA-N 0.000 description 2
- FOXGCSWJHNGAHI-UHFFFAOYSA-N 6-(dimethylamino)-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound N1=CNC(=O)C2=C1C=NC(N(C)C)=C2 FOXGCSWJHNGAHI-UHFFFAOYSA-N 0.000 description 2
- BBPUOYYUBFLNML-UHFFFAOYSA-N 6-chloro-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound N1=CNC(=O)C2=C1C=NC(Cl)=C2 BBPUOYYUBFLNML-UHFFFAOYSA-N 0.000 description 2
- IMVBSHGHRSHNOT-UHFFFAOYSA-N 6-phenylmethoxy-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound C1=C2C(=O)NC=NC2=CN=C1OCC1=CC=CC=C1 IMVBSHGHRSHNOT-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 101100503636 Danio rerio fyna gene Proteins 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 101150018272 FYN gene Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- OBICOKSTJBXYFN-UHFFFAOYSA-N N,N-dimethyl-4-nitro-2H-pyridin-1-amine Chemical compound CN(N1CC=C(C=C1)[N+](=O)[O-])C OBICOKSTJBXYFN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- RNCGDMXTBBJFEB-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(1-methyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1CC(C)(CO2)COC12C(O1)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 RNCGDMXTBBJFEB-UHFFFAOYSA-N 0.000 description 2
- YCPVGYFQXXTANI-UHFFFAOYSA-N n-(2-benzyl-3h-benzimidazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1N=2)=CC=C1NC=2CC1=CC=CC=C1 YCPVGYFQXXTANI-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000003566 phosphorylation assay Methods 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- DMOYILRVNNYQTM-UHFFFAOYSA-N tributyl-[5-(1-methyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)furan-2-yl]stannane Chemical compound O1C([Sn](CCCC)(CCCC)CCCC)=CC=C1C1(OC2)OCC2(C)CO1 DMOYILRVNNYQTM-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical group C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- BCXOSCQTHVTUET-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC=C1F BCXOSCQTHVTUET-UHFFFAOYSA-N 0.000 description 1
- JXYVDGXOCFQXTF-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=NC=C1 JXYVDGXOCFQXTF-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- DDCMQWDHBVDKHH-UHFFFAOYSA-N 1-[(2,3-difluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC(F)=C1F DDCMQWDHBVDKHH-UHFFFAOYSA-N 0.000 description 1
- ZEGHCBNPNZAANE-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC(F)=CC(F)=C1 ZEGHCBNPNZAANE-UHFFFAOYSA-N 0.000 description 1
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
- NJZQOCCEDXRQJM-UHFFFAOYSA-N 1-benzylindole Chemical compound C1=CC2=CC=CC=C2N1CC1=CC=CC=C1 NJZQOCCEDXRQJM-UHFFFAOYSA-N 0.000 description 1
- YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical compound C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- NQRIHPCAOWTVBX-UHFFFAOYSA-N 2-[[2-(methanesulfonamido)ethylamino]-[(2-methylsulfinylethylamino)-(3-methylsulfinylpropylamino)-(3-methylsulfonylpropylamino)methyl]amino]-2-(2-methylsulfonylethylamino)acetamide Chemical compound CS(=O)CCCNC(NCCCS(C)(=O)=O)(NCCS(C)=O)N(NCCNS(C)(=O)=O)C(NCCS(C)(=O)=O)C(N)=O NQRIHPCAOWTVBX-UHFFFAOYSA-N 0.000 description 1
- WOBMUXLADQPSBY-UHFFFAOYSA-N 2-benzyl-5-nitro-1,3-dihydroindazole Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2NN1CC1=CC=CC=C1 WOBMUXLADQPSBY-UHFFFAOYSA-N 0.000 description 1
- LIEPVGBDUYKPLC-UHFFFAOYSA-N 2-chloro-4-nitropyridine Chemical compound [O-][N+](=O)C1=CC=NC(Cl)=C1 LIEPVGBDUYKPLC-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 description 1
- KQAODTJBTYIOOT-UHFFFAOYSA-N 3-(benzenesulfonyl)-6-nitro-1h-indole Chemical compound C=1NC2=CC([N+](=O)[O-])=CC=C2C=1S(=O)(=O)C1=CC=CC=C1 KQAODTJBTYIOOT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FWXAUDSWDBGCMN-UHFFFAOYSA-N 3-diphenylphosphanylbutan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 FWXAUDSWDBGCMN-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical group ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 description 1
- GREQVLMAOPEZJS-UHFFFAOYSA-N 4-n-[1-(benzenesulfonyl)indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 GREQVLMAOPEZJS-UHFFFAOYSA-N 0.000 description 1
- HNAHOJSTZQCTPU-UHFFFAOYSA-N 4-n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1F HNAHOJSTZQCTPU-UHFFFAOYSA-N 0.000 description 1
- DCOMGRGZHXGGEZ-UHFFFAOYSA-N 4-n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC(F)=C1 DCOMGRGZHXGGEZ-UHFFFAOYSA-N 0.000 description 1
- MGPVJZYEBBTLTF-UHFFFAOYSA-N 4-n-[1-[(4-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=C(F)C=C1 MGPVJZYEBBTLTF-UHFFFAOYSA-N 0.000 description 1
- BGLXNPQDKXFUFO-UHFFFAOYSA-N 4-n-[3-(benzenesulfonyl)-1h-indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C12)=CC=C1NC=C2S(=O)(=O)C1=CC=CC=C1 BGLXNPQDKXFUFO-UHFFFAOYSA-N 0.000 description 1
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 1
- WSGURAYTCUVDQL-UHFFFAOYSA-N 5-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C2NN=CC2=C1 WSGURAYTCUVDQL-UHFFFAOYSA-N 0.000 description 1
- OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
- UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 description 1
- NUTUPYCNXAFILA-UHFFFAOYSA-N 6-chloro-1h-pyrido[3,4-d]pyrimidin-2-one Chemical compound C1=NC(=O)NC2=C1C=C(Cl)N=C2 NUTUPYCNXAFILA-UHFFFAOYSA-N 0.000 description 1
- OGOPAVRSPJYRLS-UHFFFAOYSA-N 6-chloropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1 OGOPAVRSPJYRLS-UHFFFAOYSA-N 0.000 description 1
- HJYSSQUVGIUOHP-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-2-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=N1 HJYSSQUVGIUOHP-UHFFFAOYSA-N 0.000 description 1
- YMLCINFVTBZDSD-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-3-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CN=C1 YMLCINFVTBZDSD-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 206010061968 Gastric neoplasm Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 1
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000187213 Streptomyces limosus Species 0.000 description 1
- 241000320554 Streptomyces rimosus subsp. paromomycinus Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000002355 alkine group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000000320 amidine group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000002942 anti-growth Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000005418 aryl aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- MSJHOJKVMMEMNX-UHFFFAOYSA-N benzylhydrazine;hydron;dichloride Chemical compound Cl.Cl.NNCC1=CC=CC=C1 MSJHOJKVMMEMNX-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical group C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000002338 cryopreservative effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- UZXVIZOKQMXWKF-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(3-methylimidazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CN1C=NC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 UZXVIZOKQMXWKF-UHFFFAOYSA-N 0.000 description 1
- DFZVDCVWUGWYOF-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 DFZVDCVWUGWYOF-UHFFFAOYSA-N 0.000 description 1
- XCOAATZYXZVAHA-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 XCOAATZYXZVAHA-UHFFFAOYSA-N 0.000 description 1
- AWXQTMDKUGQPCQ-UHFFFAOYSA-N n-(1-benzylindol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=C2)=CC=C1N2CC1=CC=CC=C1 AWXQTMDKUGQPCQ-UHFFFAOYSA-N 0.000 description 1
- BWFFCJKMJCRFNE-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=C(F)C=CC=2)N=C2)C2=C1 BWFFCJKMJCRFNE-UHFFFAOYSA-N 0.000 description 1
- BYYXZSVUFYEWRK-UHFFFAOYSA-N n-ethylaniline;hydron;chloride Chemical compound Cl.CCNC1=CC=CC=C1 BYYXZSVUFYEWRK-UHFFFAOYSA-N 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003585 oxepinyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- 150000008518 pyridopyrimidines Chemical class 0.000 description 1
- 125000005554 pyridyloxy group Chemical group 0.000 description 1
- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000021014 regulation of cell growth Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000005306 thianaphthenyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
- OGYWKJKAIAEDQX-UHFFFAOYSA-N tributyl-(3-methylimidazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=CN1C OGYWKJKAIAEDQX-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9614763.2A GB9614763D0 (en) | 1996-07-13 | 1996-07-13 | Heterocyclic compounds |
| GB9614763.2 | 1996-07-13 | ||
| GB9625492.5 | 1996-12-07 | ||
| GBGB9625492.5A GB9625492D0 (en) | 1996-12-07 | 1996-12-07 | Heterocyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20000023812A true KR20000023812A (ko) | 2000-04-25 |
Family
ID=26309694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019997000298A Withdrawn KR20000023812A (ko) | 1996-07-13 | 1999-01-13 | 단백질 티로신 키나제의 억제제인 비시클릭 헤테로방향족 화합물 |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US6174889B1 (enExample) |
| EP (2) | EP0912570B1 (enExample) |
| JP (1) | JP2000514445A (enExample) |
| KR (1) | KR20000023812A (enExample) |
| CN (1) | CN1230187A (enExample) |
| AP (1) | AP9901434A0 (enExample) |
| AR (1) | AR007856A1 (enExample) |
| AT (1) | ATE249458T1 (enExample) |
| AU (1) | AU3443997A (enExample) |
| BR (1) | BR9710359A (enExample) |
| CA (1) | CA2260061A1 (enExample) |
| CZ (1) | CZ8999A3 (enExample) |
| DE (1) | DE69724789T2 (enExample) |
| EA (1) | EA199900022A1 (enExample) |
| ES (1) | ES2206729T3 (enExample) |
| HR (1) | HRP970371A2 (enExample) |
| ID (1) | ID19403A (enExample) |
| IL (1) | IL127796A0 (enExample) |
| IS (1) | IS4939A (enExample) |
| NO (1) | NO990124L (enExample) |
| PE (1) | PE91198A1 (enExample) |
| PL (1) | PL331221A1 (enExample) |
| TR (1) | TR199900049T2 (enExample) |
| WO (1) | WO1998002438A1 (enExample) |
| YU (1) | YU1099A (enExample) |
Families Citing this family (292)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU719434B2 (en) | 1996-02-13 | 2000-05-11 | Astrazeneca Ab | Quinazoline derivatives as VEGF inhibitors |
| AU719327B2 (en) | 1996-03-05 | 2000-05-04 | Astrazeneca Ab | 4-anilinoquinazoline derivatives |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| EA005889B1 (ru) | 1997-11-11 | 2005-06-30 | Пфайзер Продактс Инк. | Производные тиенопиримидина и тиенопиридина, полезные в качестве противораковых агентов |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| JP4666762B2 (ja) | 1998-06-19 | 2011-04-06 | ファイザー・プロダクツ・インク | ピロロ［２．３−ｄ］ピリミジン化合物 |
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| BRPI9914164B8 (pt) | 1998-09-29 | 2021-05-25 | American Cyanamid Co | compostos de 3-ciano quinolina |
| US6288082B1 (en) | 1998-09-29 | 2001-09-11 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| NZ510551A (en) * | 1998-09-29 | 2003-03-28 | American Cyanamid Co | Substituted 3-cyanoquinolines useful as protein tyrosine kinases inhibitors |
| US7393823B1 (en) | 1999-01-20 | 2008-07-01 | Oregon Health And Science University | HER-2 binding antagonists |
| US7396810B1 (en) * | 2000-08-14 | 2008-07-08 | Oregon Health Sciences University | Compositions and methods for treating cancer by modulating HER-2 and EGF receptors |
| US7625859B1 (en) * | 2000-02-16 | 2009-12-01 | Oregon Health & Science University | HER-2 binding antagonists |
| JP3270834B2 (ja) | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| GB9914486D0 (en) | 1999-06-21 | 1999-08-18 | Smithkline Beecham Plc | Medicaments |
| US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| AU5783300A (en) | 1999-07-09 | 2001-01-30 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| GB9917408D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| GB9917406D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
| US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
| AU769222B2 (en) | 1999-11-05 | 2004-01-22 | Genzyme Corporation | Quinazoline derivatives as VEGF inhibitors |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| UA75055C2 (uk) * | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
| DK1235830T3 (da) | 1999-12-10 | 2004-03-29 | Pfizer Prod Inc | Pyrrolo[2,3-d]pyrimidin-forbindelser som proteinkinaseinhibitorer |
| AR029423A1 (es) | 1999-12-21 | 2003-06-25 | Sugen Inc | Compuesto derivado de pirrolo-[pirimidin o piridin]-6-ona, metodo de preparacion de dichos compuestos, composiciones farmaceuticas que los comprenden, un metodo para regular, modular o inhibir la actividad de la proteina quinasa y un metodo de tratar o prevenir una enfermedad de mamiferos |
| AU784297C (en) | 2000-06-26 | 2007-01-11 | Pfizer Products Inc. | Pyrrolo(2,3-d)pyrimidine compounds as immunosuppressive agents |
| CN1305872C (zh) * | 2000-06-30 | 2007-03-21 | 葛兰素集团有限公司 | 喹唑啉类化合物的制备方法 |
| IL154107A0 (en) * | 2000-07-26 | 2003-07-31 | Smithkline Beecham Plc | Aminopiperidine quinolines and their azaisosteric analogues with antibacterial activity |
| BR0113078A (pt) * | 2000-08-09 | 2003-07-01 | Astrazeneca Ab | Uso de um composto, composto, processo para a preparação do mesmo, composição farmacêutica, e, método para produzir um efeito antiangiogênico e/ou redutor da permeabilidade vascular em um animal de sangue quente |
| PL359920A1 (en) | 2000-09-20 | 2004-09-06 | Merck Patent Gmbh | 4-amino-quinazolines |
| MX242553B (es) | 2000-10-20 | 2006-12-06 | Eisai Co Ltd | Derivados aromaticos que contienen nitrogeno. |
| SG138469A1 (en) | 2001-01-05 | 2008-01-28 | Pfizer | Antibodies to insulin-like growth factor i receptor |
| EP1353693B1 (en) | 2001-01-16 | 2005-03-16 | Glaxo Group Limited | Pharmaceutical combination containing a 4-quinazolineamine and paclitaxel, carboplatin or vinorelbine for the treatment of cancer |
| GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| ATE330956T1 (de) | 2001-04-13 | 2006-07-15 | Pfizer Prod Inc | Bizyklisch substituierte 4- aminopyridopyrimidinderivate |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US7301023B2 (en) | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
| US6995171B2 (en) | 2001-06-21 | 2006-02-07 | Agouron Pharmaceuticals, Inc. | Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents |
| US7829566B2 (en) | 2001-09-17 | 2010-11-09 | Werner Mederski | 4-amino-quinazolines |
| AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| EP1465900B1 (en) | 2002-01-10 | 2008-05-14 | Bayer HealthCare AG | Rho-kinase inhibitors |
| TW200406390A (en) * | 2002-01-17 | 2004-05-01 | Neurogen Corp | Substituted quinazolin-4-ylamine analogues |
| JP4423043B2 (ja) | 2002-01-23 | 2010-03-03 | バイエル ファーマセチカル コーポレーション | Ｒｈｏ−キナーゼ阻害剤 |
| EP1470121B1 (en) | 2002-01-23 | 2012-07-11 | Bayer HealthCare LLC | Pyrimidine derivatives as rho-kinase inhibitors |
| WO2003064421A1 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine derivatives |
| AU2003239302A1 (en) | 2002-01-29 | 2003-09-02 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| JP2005527511A (ja) | 2002-03-01 | 2005-09-15 | ファイザー インコーポレイテッド | 抗血管形成剤として有用なチエノピリジンのインドリル−尿素誘導体およびその使用法 |
| US20050176740A1 (en) * | 2002-04-08 | 2005-08-11 | Spector Neil L. | Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor |
| UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
| EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| AU2003251009A1 (en) * | 2002-07-15 | 2004-02-02 | Janssen Pharmaceutica N.V. | 3-phenyl analogs of toxoflavine as kinase inhibitors |
| ATE360015T1 (de) * | 2002-07-31 | 2007-05-15 | Critical Outcome Technologies | Protein tyrosin kinase inhibitoren |
| ATE380810T1 (de) * | 2002-10-09 | 2007-12-15 | Critical Outcome Technologies | Protein-tyrosine-kinase-inhibitoren |
| FR2846657B1 (fr) * | 2002-11-05 | 2004-12-24 | Servier Lab | Nouveaux composes pyridopyrimidinone, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP4611745B2 (ja) | 2002-11-20 | 2011-01-12 | アレイ バイオファーマ、インコーポレイテッド | ＥｒｂＢ２及びＥＧＦＲ阻害剤としてのシアノグアニジン及びシアノアミジン |
| PL378246A1 (pl) | 2002-11-26 | 2006-03-20 | Pfizer Products Inc. | Sposób leczenia odrzucania przeszczepu |
| WO2004055004A1 (en) * | 2002-12-13 | 2004-07-01 | Neurogen Corporation | Carboxylic acid, phosphate or phosphonate substituted quinazolin-4-ylamine analogues as capsaicin receptor modulators |
| HRP20050559A2 (en) | 2002-12-19 | 2006-02-28 | Pfizer Inc. | 2-(1h-indazole-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophthalmic diseases |
| OA13309A (en) | 2002-12-20 | 2007-04-13 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth. |
| DK2476667T3 (da) | 2003-02-26 | 2014-09-15 | Sugen Inc | Aminoheteroaryl-forbindelser som proteinkinase-inhibitorer |
| AU2004265226A1 (en) * | 2003-05-16 | 2005-02-24 | Receptor Biologix, Inc. | Intron fusion proteins, and methods of identifying and using same |
| TW200510373A (en) * | 2003-07-14 | 2005-03-16 | Neurogen Corp | Substituted quinolin-4-ylamine analogues |
| US7329664B2 (en) * | 2003-07-16 | 2008-02-12 | Neurogen Corporation | Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues |
| US7008953B2 (en) | 2003-07-30 | 2006-03-07 | Agouron Pharmaceuticals, Inc. | 3, 5 Disubstituted indazole compounds, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation |
| US20060204966A1 (en) * | 2003-08-01 | 2006-09-14 | Spector Neil L | Treatment of cancers expressing p95 erbb2 |
| HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| US20050038047A1 (en) * | 2003-08-14 | 2005-02-17 | Edwards Paul John | Azaquinazoline derivatives |
| CA2536321A1 (en) | 2003-08-29 | 2005-03-10 | Pfizer Inc. | Thienopyridine-phenylacet amides and their derivatives useful as new anti-angiogenic agents |
| US20070105865A1 (en) * | 2003-09-09 | 2007-05-10 | Neurogen Corporation | Substituted bicyclic quinazolin-4-ylamine derivatives |
| AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
| EP2210607B1 (en) | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
| WO2005044788A1 (ja) | 2003-11-11 | 2005-05-19 | Eisai Co., Ltd. | ウレア誘導体およびその製造方法 |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| DK1689721T3 (da) * | 2003-11-26 | 2010-09-20 | Pfizer Prod Inc | Aminopyrazolderivater som GSK-3-ihibitorer |
| SG141459A1 (en) | 2003-12-23 | 2008-04-28 | Pfizer | Novel quinoline derivatives |
| TW200529846A (en) | 2004-02-20 | 2005-09-16 | Wyeth Corp | 3-quinolinecarbonitrile protein kinase inhibitors |
| KR20080095915A (ko) | 2004-05-06 | 2008-10-29 | 워너-램버트 캄파니 엘엘씨 | 4-페닐아미노-퀴나졸린-6-일-아미드 |
| WO2005113596A2 (en) * | 2004-05-14 | 2005-12-01 | Receptor Biologix, Inc. | Cell surface receptor isoforms and methods of identifying and using the same |
| AU2005251735A1 (en) * | 2004-06-04 | 2005-12-22 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| CN101014365B (zh) | 2004-07-16 | 2011-04-13 | 辉瑞产品公司 | 使用抗-igf-1r抗体联合治疗非血液的恶性肿瘤 |
| DE602005020465D1 (de) | 2004-08-26 | 2010-05-20 | Pfizer | Enantiomerenreine aminoheteroaryl-verbindungen als proteinkinasehemmer |
| JP4834553B2 (ja) | 2004-09-17 | 2011-12-14 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 医薬組成物 |
| US20080206231A1 (en) * | 2004-10-05 | 2008-08-28 | Oregon Health And Science University | Compositions and Methods for Treating Disease |
| TW200621251A (en) | 2004-10-12 | 2006-07-01 | Neurogen Corp | Substituted biaryl quinolin-4-ylamine analogues |
| CN101124228B (zh) | 2004-12-14 | 2011-06-15 | 阿斯利康(瑞典)有限公司 | 用作抗肿瘤药物的吡唑并嘧啶化合物 |
| GB0428475D0 (en) * | 2004-12-30 | 2005-02-02 | 4 Aza Bioscience Nv | Pyrido(3,2-D)pyrimidine derivatives and pharmaceutical compositions useful as medicines for the treatment of autoimmune disorders |
| AU2006230563B8 (en) | 2005-03-31 | 2010-06-17 | Agensys, Inc. | Antibodies and related molecules that bind to 161P2F10B proteins |
| AU2006238930B2 (en) | 2005-04-26 | 2010-12-23 | Pfizer Inc. | P-cadherin antibodies |
| US20090170769A1 (en) * | 2005-05-13 | 2009-07-02 | Pei Jin | Cell surface receptor isoforms and methods of identifying and using the same |
| AU2006261607A1 (en) * | 2005-06-24 | 2006-12-28 | Gilead Sciences, Inc. | Pyrido(3,2-d)pyrimidines and pharmaceutical compositions useful for treating hepatitis C. |
| JP4989476B2 (ja) | 2005-08-02 | 2012-08-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質の効果を検定する方法 |
| TWI387592B (zh) | 2005-08-30 | 2013-03-01 | Novartis Ag | 經取代之苯并咪唑及其作為與腫瘤形成相關激酶之抑制劑之方法 |
| NZ566774A (en) | 2005-09-07 | 2011-11-25 | Pfizer | Human monoclonal antibodies to activin receptor-like kinase-1 |
| DK1926996T3 (da) | 2005-09-20 | 2012-01-23 | Osi Pharmaceuticals Llc | Biologiske markører, som er prædiktive for anti-cancer-reaktion på insulinlignende vækstfaktor-1-receptorkinasehæmmere |
| EP1928861B1 (en) | 2005-09-20 | 2010-11-17 | AstraZeneca AB | 4- (ih-indazol-5-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
| RU2441869C2 (ru) | 2005-12-21 | 2012-02-10 | Эбботт Лэборетриз | Противовирусные соединения |
| WO2007076035A2 (en) | 2005-12-21 | 2007-07-05 | Abbott Laboratories | Anti-viral compounds |
| ES2395386T3 (es) | 2005-12-21 | 2013-02-12 | Abbott Laboratories | Compuestos antivirales |
| AU2007215247B2 (en) | 2006-02-10 | 2012-12-13 | Transtech Pharma, Llc | Benzazole derivatives, compositions, and methods of use as Aurora kinase inhibitors |
| JP2009527479A (ja) * | 2006-02-17 | 2009-07-30 | アバロン ファーマシューティカルズ，インコーポレイテッド | ヒドロキシピペリジン誘導体とその使用 |
| KR20090007792A (ko) | 2006-05-09 | 2009-01-20 | 화이자 프로덕츠 인크. | 시클로알킬아미노산 유도체 및 이들의 제약 조성물 |
| EP2036557B1 (en) | 2006-05-18 | 2015-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| KR100760148B1 (ko) | 2006-07-19 | 2007-09-18 | 주식회사 엘지생활건강 | 알파-리포산을 안정화시킨 화장료 조성물 |
| US8338435B2 (en) * | 2006-07-20 | 2012-12-25 | Gilead Sciences, Inc. | Substituted pyrido(3,2-D) pyrimidines and pharmaceutical compositions for treating viral infections |
| US8492378B2 (en) | 2006-08-03 | 2013-07-23 | Takeda Pharmaceutical Company Limited | GSK-3β inhibitor |
| CN101511793B (zh) | 2006-08-28 | 2011-08-03 | 卫材R&D管理有限公司 | 针对未分化型胃癌的抗肿瘤剂 |
| WO2008067119A2 (en) * | 2006-11-27 | 2008-06-05 | Smithkline Beecham Corporation | Novel compounds |
| EP2094276A4 (en) | 2006-12-20 | 2011-01-05 | Abbott Lab | ANTIVIRAL COMPOUNDS |
| US8143394B2 (en) * | 2006-12-26 | 2012-03-27 | Gilead Sciences, Inc. | Pyrido(3,2-d)pyrimidines useful for treating viral infections |
| US8637531B2 (en) * | 2006-12-26 | 2014-01-28 | Gilead Sciences, Inc. | Pyrido(3,2-d)pyridmidines useful for treating viral infections |
| TW200840584A (en) * | 2006-12-26 | 2008-10-16 | Gilead Sciences Inc | Pyrido(3,2-d)pyrimidines useful for treating viral infections |
| CA2673683C (en) | 2007-01-11 | 2014-07-29 | Critical Outcome Technologies, Inc. | Compounds and method for treatment of cancer |
| WO2008093855A1 (ja) | 2007-01-29 | 2008-08-07 | Eisai R & D Management Co., Ltd. | 未分化型胃癌治療用組成物 |
| RU2455994C2 (ru) | 2007-04-16 | 2012-07-20 | Хатчисон Медифарма Энтерпрайзис Лимитед | Пиримидиновые производные |
| GEP20125581B (en) | 2007-04-18 | 2012-07-25 | Pfizer Prod Inc | Sulfonyl amide derivatives for treatment of abnormal cell growth |
| EP2141994A4 (en) * | 2007-04-26 | 2011-05-18 | Avalon Pharmaceuticals | POLYCYCLIC COMPOUNDS AND USES THEREOF |
| MX2009012117A (es) * | 2007-05-09 | 2009-11-23 | Pfizer | Composiciones y derivados heterociclicos sustituidos y su uso farmaceutico como antibacterianos. |
| WO2009033094A2 (en) | 2007-09-07 | 2009-03-12 | Agensys, Inc. | Antibodies and related molecules that bind to 24p4c12 proteins |
| WO2009057139A2 (en) | 2007-10-29 | 2009-05-07 | Natco Pharma Limited | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents |
| EP2218712B1 (en) | 2007-11-09 | 2015-07-01 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| US8466151B2 (en) * | 2007-12-26 | 2013-06-18 | Critical Outcome Technologies, Inc. | Compounds and method for treatment of cancer |
| WO2009111644A2 (en) * | 2008-03-05 | 2009-09-11 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating pancreatic cancer |
| US8314107B2 (en) * | 2008-04-23 | 2012-11-20 | Rigel Pharmaceuticals, Inc. | Carboxamide compounds and methods for using the same |
| US7829574B2 (en) * | 2008-05-09 | 2010-11-09 | Hutchison Medipharma Enterprises Limited | Substituted quinazoline compounds and their use in treating angiogenesis-related diseases |
| US8426430B2 (en) * | 2008-06-30 | 2013-04-23 | Hutchison Medipharma Enterprises Limited | Quinazoline derivatives |
| WO2010002998A1 (en) * | 2008-07-03 | 2010-01-07 | Gilead Sciences, Inc. | 2,4,6-TRISUBSTITUTED PYRIDO (3,2-d) PYRIMIDINES USEFUL FOR TREATING VIRAL INFECTIONS |
| EP3023426A1 (en) | 2008-07-17 | 2016-05-25 | Critical Outcome Technologies, Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| ES2432414T3 (es) * | 2008-08-12 | 2013-12-03 | Glaxosmithkline Llc | Compuestos químicos |
| RS53382B (sr) | 2008-08-20 | 2014-10-31 | Zoetis Llc | Jedinjenja pirol [2,3-d]pirimidina |
| US7737157B2 (en) * | 2008-08-29 | 2010-06-15 | Hutchison Medipharma Enterprises Limited | Pyrimidine compounds |
| AR073679A1 (es) * | 2008-09-26 | 2010-11-24 | Takeda Pharmaceutical | Prevencion y tratamiento de cancer con la no expresion de lkb1 supresion o mutacion, composicion farmaceutica. usos |
| WO2010036917A1 (en) * | 2008-09-26 | 2010-04-01 | Takeda Pharmaceutical Company Limited | Prevention and treatment of cancer with ras gene mutation |
| EP2334701A4 (en) | 2008-10-16 | 2014-01-08 | Univ Pittsburgh | FULLY HUMAN ANTIBODIES AGAINST ANTIGENES ASSOCIATED WITH MELANOMA OF HIGH MOLECULAR WEIGHT AND USES THEREOF |
| US8710104B2 (en) | 2008-11-07 | 2014-04-29 | Triact Therapeutics, Inc. | Catecholic butanes and use thereof for cancer therapy |
| CN101735200B (zh) * | 2008-11-17 | 2013-01-02 | 岑均达 | 喹唑啉类化合物 |
| AU2010204619B2 (en) | 2009-01-16 | 2016-08-11 | Exelixis, Inc. | Malate salt of N-(4-{ [ 6, 7-bis (methyloxy)-quinolin-4-yl] oxy}phenyl)-N'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer |
| WO2010090764A1 (en) | 2009-02-09 | 2010-08-12 | Supergen, Inc. | Pyrrolopyrimidinyl axl kinase inhibitors |
| WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| TW201035088A (en) | 2009-02-27 | 2010-10-01 | Supergen Inc | Cyclopentathiophene/cyclohexathiophene DNA methyltransferase inhibitors |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| US8642834B2 (en) | 2009-02-27 | 2014-02-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012520893A (ja) | 2009-03-18 | 2012-09-10 | オーエスアイ・ファーマシューティカルズ，エルエルシー | Ｅｇｆｒ阻害薬及びｉｇｆ−１ｒ阻害剤の投与を含む組み合わせ癌治療 |
| AU2010273585B2 (en) | 2009-07-13 | 2015-04-23 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
| EP2459191A1 (en) | 2009-07-31 | 2012-06-06 | OSI Pharmaceuticals, LLC | Mtor inhibitor and angiogenesis inhibitor combination therapy |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| CA2772194A1 (en) | 2009-09-01 | 2011-03-10 | Pfizer Inc. | Benzimidazole derivatives |
| US20110064670A1 (en) | 2009-09-11 | 2011-03-17 | Genentech, Inc. | Method to identify a patient with an increased likelihood of responding to an anti-cancer agent |
| AU2010297344A1 (en) | 2009-09-17 | 2012-02-23 | F. Hoffmann-La Roche Ag | Methods and compositions for diagnostics use in cancer patients |
| BR112012010085B1 (pt) | 2009-10-29 | 2020-02-04 | Genosco | composto, quantidade terapeuticamente eficaz de um composto, formulação farmacêutica |
| US20120316187A1 (en) | 2009-11-13 | 2012-12-13 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| WO2011073521A1 (en) | 2009-12-15 | 2011-06-23 | Petri Salven | Methods for enriching adult-derived endothelial progenitor cells and uses thereof |
| DK3150610T3 (da) | 2010-02-12 | 2019-11-04 | Pfizer | Salte og polymorfer af 8-fluor-2-{4-[(methylamino}methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-on |
| JP2013527748A (ja) | 2010-03-03 | 2013-07-04 | オーエスアイ・ファーマシューティカルズ，エルエルシー | インスリン様増殖因子１受容体キナーゼ阻害剤に対する抗癌反応の予測に役立つ生物学的マーカー |
| EP2542893A2 (en) | 2010-03-03 | 2013-01-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| CA2794952C (en) | 2010-04-01 | 2018-05-15 | Critical Outcome Technologies Inc. | Compounds and method for treatment of hiv |
| WO2011153224A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
| US8497354B2 (en) | 2010-06-16 | 2013-07-30 | University of Pittsburgh—of the Commonwealth System of Higher Education | Antibodies to endoplasmin and their use |
| PT2975042T (pt) * | 2010-06-23 | 2019-01-11 | Hanmi Science Co Ltd | Novos derivados de pirimidina fundidos para inibição de atividade de tirosina-quinase |
| RU2560683C2 (ru) | 2010-06-25 | 2015-08-20 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое средство, задействующее соединения с ингибирующим эффектом к киназам в комбинации |
| WO2012010551A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
| KR20130126576A (ko) | 2010-07-19 | 2013-11-20 | 에프. 호프만-라 로슈 아게 | 항암요법에 반응할 가능성이 증가된 환자를 확인하는 방법 |
| JP2013538191A (ja) | 2010-07-23 | 2013-10-10 | トラスティーズ オブ ボストン ユニバーシティ | 病的血管新生および腫瘍細胞侵襲性の阻害のための治療法としてならびに分子イメージングおよび標的化送達のための抗ＤＥｓｕｐＲ阻害剤 |
| WO2012042421A1 (en) | 2010-09-29 | 2012-04-05 | Pfizer Inc. | Method of treating abnormal cell growth |
| ES2543151T3 (es) | 2010-10-20 | 2015-08-17 | Pfizer Inc | Derivados de 2-piridina como moduladores del receptor Smoothened |
| EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
| US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| US9150644B2 (en) | 2011-04-12 | 2015-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II |
| US8962650B2 (en) | 2011-04-18 | 2015-02-24 | Eisai R&D Management Co., Ltd. | Therapeutic agent for tumor |
| CA3019531A1 (en) | 2011-04-19 | 2012-10-26 | Pfizer Inc. | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
| US9896730B2 (en) | 2011-04-25 | 2018-02-20 | OSI Pharmaceuticals, LLC | Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment |
| JP6038128B2 (ja) | 2011-06-03 | 2016-12-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー |
| HUE052198T2 (hu) | 2011-07-21 | 2021-04-28 | Sumitomo Dainippon Pharma Oncology Inc | Heterociklusos protein kináz inhibitorok |
| US20130084286A1 (en) | 2011-08-31 | 2013-04-04 | Thomas E. Januario | Diagnostic markers |
| EP2758402B9 (en) | 2011-09-22 | 2016-09-14 | Pfizer Inc | Pyrrolopyrimidine and purine derivatives |
| JP2014531213A (ja) | 2011-09-30 | 2014-11-27 | ジェネンテック， インコーポレイテッド | 上皮又は間葉の表現型の診断用メチル化マーカー、及び腫瘍又は腫瘍細胞におけるｅｇｆｒキナーゼ阻害薬に対する応答 |
| CA2848842C (en) | 2011-10-04 | 2020-09-29 | King's College London | Ige anti -hmw-maa antibody |
| EP2776467A1 (en) | 2011-11-08 | 2014-09-17 | Pfizer Inc | Methods of treating inflammatory disorders using anti-m-csf antibodies |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
| JP6243918B2 (ja) | 2012-10-16 | 2017-12-06 | トレロ ファーマシューティカルズ， インコーポレイテッド | Ｐｋｍ２調節因子およびそれらの使用方法 |
| US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
| US9334239B2 (en) | 2012-12-21 | 2016-05-10 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス，インク． | 癌治療 |
| TR201911151T4 (tr) | 2013-03-14 | 2019-08-21 | Tolero Pharmaceuticals Inc | Jak2 ve alk2 inhibitörleri ve bunların kullanım yöntemleri. |
| ES2644828T3 (es) * | 2013-03-15 | 2017-11-30 | Quanticel Pharmaceuticals Inc | Inhibidores de histona desmetilasa |
| EP2976085A1 (en) | 2013-03-21 | 2016-01-27 | INSERM - Institut National de la Santé et de la Recherche Médicale | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
| US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
| MX368099B (es) | 2013-05-14 | 2019-09-19 | Eisai R&D Man Co Ltd | Biomarcadores para predecir y evaluar el grado de respuesta de sujetos con cancer de endometrio a compuestos de tipo lenvatinib. |
| AR096654A1 (es) | 2013-06-20 | 2016-01-27 | Ab Science | Derivados de benzimidazol como inhibidores selectivos de proteína quinasa |
| CA2923667A1 (en) | 2013-09-09 | 2015-03-12 | Triact Therapeutics, Inc. | Cancer therapy |
| UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
| ES2896404T3 (es) | 2014-04-04 | 2022-02-24 | Crown Bioscience Inc Taicang | Métodos para determinar la capacidad de respuesta a inhibidores de MEK/ERK |
| WO2015156674A2 (en) | 2014-04-10 | 2015-10-15 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
| CN106232598B (zh) | 2014-04-30 | 2020-03-13 | 辉瑞公司 | 环烷基-连接的二杂环衍生物 |
| WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
| ES2925224T3 (es) | 2014-07-31 | 2022-10-14 | Us Gov Health & Human Services | Anticuerpos monoclonales humanos contra EphA4 y su uso |
| JP6659554B2 (ja) | 2014-08-28 | 2020-03-04 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 高純度キノリン誘導体およびその製造方法 |
| JP6621477B2 (ja) | 2014-12-18 | 2019-12-18 | ファイザー・インク | ピリミジンおよびトリアジン誘導体ならびにａｘｌ阻害薬としてのそれらの使用 |
| RU2739942C2 (ru) | 2014-12-24 | 2020-12-30 | Дженентек, Инк. | Терапевтические, диагностические и прогностические способы для рака мочевого пузыря |
| HUE064614T2 (hu) | 2015-02-25 | 2024-04-28 | Eisai R&D Man Co Ltd | Eljárás egy kinolin-származék keserû ízének elnyomására |
| KR20240064733A (ko) | 2015-03-04 | 2024-05-13 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| MX2017013383A (es) | 2015-04-20 | 2017-12-07 | Tolero Pharmaceuticals Inc | Prediccion de respuesta a alvocidib mediante perfilado mitocondrial. |
| WO2016178876A2 (en) | 2015-05-01 | 2016-11-10 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
| MX380798B (es) | 2015-05-18 | 2025-03-12 | Sumitomo Pharma Oncology Inc | Profármacos de alvocidib que tienen una biodisponibilidad aumentada. |
| BR112017027227B1 (pt) | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
| WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
| JP7083497B2 (ja) | 2015-08-03 | 2022-06-13 | スミトモ ファーマ オンコロジー， インコーポレイテッド | がんの処置のための併用療法 |
| JP6553726B2 (ja) | 2015-08-20 | 2019-07-31 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| EP3383375A1 (en) | 2015-12-03 | 2018-10-10 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
| WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| EP3362471B1 (en) | 2016-12-19 | 2021-11-17 | Sumitomo Dainippon Pharma Oncology, Inc. | Profiling peptides and methods for sensitivity profiling |
| WO2018119183A2 (en) | 2016-12-22 | 2018-06-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| KR102539920B1 (ko) | 2017-02-08 | 2023-06-05 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양-치료용 약제학적 조성물 |
| US20200197384A1 (en) | 2017-05-16 | 2020-06-25 | Eisai R&D Management Co., Ltd. | Treatment of hepatocellular carcinoma |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| MX2020002502A (es) | 2017-09-08 | 2020-07-20 | Amgen Inc | Inhibidores de kras g12c y metodos para utilizarlos. |
| US11497756B2 (en) | 2017-09-12 | 2022-11-15 | Sumitomo Pharma Oncology, Inc. | Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib |
| WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
| MX2020010836A (es) | 2018-05-04 | 2021-01-08 | Amgen Inc | Inhibidores de kras g12c y métodos para su uso. |
| JP7361722B2 (ja) | 2018-05-04 | 2023-10-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤及び同一物の使用方法 |
| ES2986917T3 (es) | 2018-05-10 | 2024-11-13 | Amgen Inc | Inhibidores de KRAS G12C para el tratamiento del cáncer |
| CA3098885A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| CA3099799A1 (en) | 2018-06-11 | 2019-12-19 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
| WO2020050890A2 (en) | 2018-06-12 | 2020-03-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| JP2021530554A (ja) | 2018-07-26 | 2021-11-11 | スミトモ ダイニッポン ファーマ オンコロジー， インコーポレイテッド | 異常なａｃｖｒ１発現を伴う疾患を処置するための方法およびそこで使用するためのａｃｖｒ１阻害剤 |
| BR112021005082A2 (pt) | 2018-09-18 | 2021-06-08 | Nikang Therapeutics, Inc. | derivados de anel tricíclico fundido como inibidores de src homologia-2 fosfatase |
| JP2022512584A (ja) | 2018-10-04 | 2022-02-07 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 角皮症を処置するためのｅｇｆｒインヒビター |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| AU2019384118B2 (en) | 2018-11-19 | 2025-06-12 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| CA3119807A1 (en) | 2018-12-04 | 2020-06-11 | Sumitomo Dainippon Pharma Oncology, Inc. | Cdk9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
| EA202191730A1 (ru) | 2018-12-20 | 2021-08-24 | Эмджен Инк. | Ингибиторы kif18a |
| MX2021007104A (es) | 2018-12-20 | 2021-08-11 | Amgen Inc | Inhibidores de kif18a. |
| US12441736B2 (en) | 2018-12-20 | 2025-10-14 | Amgen Inc. | KIF18A inhibitors |
| MA54546A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a |
| NL2022471B1 (en) | 2019-01-29 | 2020-08-18 | Vationpharma B V | Solid state forms of oclacitinib |
| US11471456B2 (en) | 2019-02-12 | 2022-10-18 | Sumitomo Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
| US20230096028A1 (en) | 2019-03-01 | 2023-03-30 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
| CA3130080A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| JP2022525149A (ja) | 2019-03-20 | 2022-05-11 | スミトモ ダイニッポン ファーマ オンコロジー， インコーポレイテッド | ベネトクラクスが失敗した急性骨髄性白血病（ａｍｌ）の処置 |
| CN113747895A (zh) | 2019-03-22 | 2021-12-03 | 大日本住友制药肿瘤公司 | 包含pkm2调节剂的组合物和用其治疗的方法 |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| PH12021552922A1 (en) | 2019-05-21 | 2022-04-04 | Amgen Inc | Solid state forms |
| EP4007756A1 (en) | 2019-08-02 | 2022-06-08 | Amgen Inc. | Kif18a inhibitors |
| CA3147272A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| EP4007752B1 (en) | 2019-08-02 | 2025-09-24 | Amgen Inc. | Kif18a inhibitors |
| US20220372018A1 (en) | 2019-08-02 | 2022-11-24 | Amgen Inc. | Kif18a inhibitors |
| EP4048671A1 (en) | 2019-10-24 | 2022-08-31 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| CR20220240A (es) | 2019-11-04 | 2022-08-03 | Revolution Medicines Inc | Inhibidores de ras |
| CN114786777A (zh) | 2019-11-04 | 2022-07-22 | 锐新医药公司 | Ras抑制剂 |
| PH12022550988A1 (en) | 2019-11-04 | 2023-10-09 | Revolution Medicines Inc | Ras inhibitors |
| US20210139517A1 (en) | 2019-11-08 | 2021-05-13 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| MX2022005726A (es) | 2019-11-14 | 2022-06-09 | Amgen Inc | Sintesis mejorada del compuesto inhibidor de g12c de kras. |
| KR20220101125A (ko) | 2019-11-14 | 2022-07-19 | 암젠 인크 | Kras g12c 억제제 화합물의 개선된 합성 |
| WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| MX2022008305A (es) | 2020-01-07 | 2022-08-08 | Revolution Medicines Inc | Dosificacion de inhibidores de shp2 y metodos de tratamiento del cancer. |
| WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
| TW202214253A (zh) | 2020-06-18 | 2022-04-16 | 美商銳新醫藥公司 | 延遲、預防及治療對ｒａｓ抑制劑之後天抗性之方法 |
| CN116209438A (zh) | 2020-09-03 | 2023-06-02 | 锐新医药公司 | 使用sos1抑制剂治疗具有shp2突变的恶性疾病 |
| EP4214209A1 (en) | 2020-09-15 | 2023-07-26 | Revolution Medicines, Inc. | Indole derivatives as ras inhibitors in the treatment of cancer |
| AU2021409816A1 (en) | 2020-12-22 | 2023-07-06 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
| JP7696443B2 (ja) | 2021-04-13 | 2025-06-20 | ヌバレント， インク． | Ｅｇｆｒ変異を有するがんを処置するためのアミノ置換ヘテロ環類 |
| EP4334325A1 (en) | 2021-05-05 | 2024-03-13 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
| EP4334324A1 (en) | 2021-05-05 | 2024-03-13 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| CN118561952A (zh) | 2021-05-05 | 2024-08-30 | 锐新医药公司 | Ras抑制剂 |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| JP2025500878A (ja) | 2021-12-17 | 2025-01-15 | ジェンザイム・コーポレーション | Ｓｈｐ２阻害剤としてのピラゾロピラジン化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| JP2025509217A (ja) | 2022-03-07 | 2025-04-11 | アムジエン・インコーポレーテツド | ４－メチル－２－プロパン－２－イル－ピリジン－３－カルボニトリルを調製するための方法 |
| JP2025510572A (ja) | 2022-03-08 | 2025-04-15 | レボリューション メディシンズ インコーポレイテッド | 免疫不応性肺癌を治療するための方法 |
| AU2023285116A1 (en) | 2022-06-10 | 2024-12-19 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| CN120359029A (zh) | 2022-10-14 | 2025-07-22 | 黑钻治疗公司 | 使用异喹啉或6-氮杂-喹啉衍生物治疗癌症的方法 |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| AU2024252105A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| CN121100123A (zh) | 2023-04-14 | 2025-12-09 | 锐新医药公司 | Ras抑制剂的结晶形式 |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025137507A1 (en) | 2023-12-22 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Sos1 inhibitors and uses thereof |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5600M (enExample) * | 1966-07-19 | 1968-01-08 | ||
| WO1991018921A1 (en) * | 1990-05-25 | 1991-12-12 | Georgetown University | GROWTH FACTOR WHICH INHIBITS THE GROWTH OF CELLS OVEREXPRESSING THE HUMAN ONCOGENE erbB-2 |
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
| US5654307A (en) * | 1994-01-25 | 1997-08-05 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
| IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| WO1995024190A2 (en) | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| TW414798B (en) | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (enExample) | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| FI971953A7 (fi) | 1994-11-14 | 1997-05-12 | Warner Lambert Co | Proteiinityrosiinikinaasin välittämää soluproliferaatiota inhiboivat 6 -aryyli-pyrido(2,3-d)pyrimidiinit ja naftyridiinit |
| GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| BR9607089A (pt) * | 1995-11-14 | 1997-11-11 | Pharmacia & Upjohn Spa | Compostos de pirimidina condensada biciclica composição farmacéutica utilização e produtos que contém os mesmos e processo para a preparação desses compostos |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| ID19430A (id) | 1996-07-13 | 1998-07-09 | Glaxo Group Ltd | Senyawa senyawa heterosiklik |
| AR007857A1 (es) | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios uso en medicina ycomposiciones farmaceuticas que los contienen. |
| IL129825A0 (en) * | 1996-11-27 | 2000-02-29 | Pfizer | Fused bicyclic pyrimidine derivatives |
-
1997
- 1997-07-08 HR HR9625492.5A patent/HRP970371A2/hr not_active Application Discontinuation
- 1997-07-11 EP EP97930518A patent/EP0912570B1/en not_active Expired - Lifetime
- 1997-07-11 CZ CZ9989A patent/CZ8999A3/cs unknown
- 1997-07-11 ID IDP972412A patent/ID19403A/id unknown
- 1997-07-11 YU YU1099A patent/YU1099A/sr unknown
- 1997-07-11 AR ARP970103102A patent/AR007856A1/es unknown
- 1997-07-11 DE DE69724789T patent/DE69724789T2/de not_active Expired - Fee Related
- 1997-07-11 EA EA199900022A patent/EA199900022A1/ru unknown
- 1997-07-11 BR BR9710359A patent/BR9710359A/pt not_active Application Discontinuation
- 1997-07-11 JP JP10505598A patent/JP2000514445A/ja not_active Ceased
- 1997-07-11 TR TR1999/00049T patent/TR199900049T2/xx unknown
- 1997-07-11 PL PL97331221A patent/PL331221A1/xx unknown
- 1997-07-11 IL IL12779697A patent/IL127796A0/xx unknown
- 1997-07-11 US US09/214,270 patent/US6174889B1/en not_active Expired - Fee Related
- 1997-07-11 AP APAP/P/1999/001434A patent/AP9901434A0/en unknown
- 1997-07-11 AT AT97930518T patent/ATE249458T1/de not_active IP Right Cessation
- 1997-07-11 PE PE1997000611A patent/PE91198A1/es not_active Application Discontinuation
- 1997-07-11 CA CA002260061A patent/CA2260061A1/en not_active Abandoned
- 1997-07-11 WO PCT/EP1997/003674 patent/WO1998002438A1/en not_active Ceased
- 1997-07-11 AU AU34439/97A patent/AU3443997A/en not_active Abandoned
- 1997-07-11 ES ES97930518T patent/ES2206729T3/es not_active Expired - Lifetime
- 1997-07-11 CN CN97197876A patent/CN1230187A/zh active Pending
- 1997-07-11 EP EP02080417A patent/EP1304110A3/en not_active Withdrawn
-
1998
- 1998-12-31 IS IS4939A patent/IS4939A/is unknown
-
1999
- 1999-01-12 NO NO990124A patent/NO990124L/no not_active Application Discontinuation
- 1999-01-13 KR KR1019997000298A patent/KR20000023812A/ko not_active Withdrawn
-
2000
- 2000-06-30 US US09/608,971 patent/US6723726B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IL127796A0 (en) | 1999-10-28 |
| AR007856A1 (es) | 1999-11-24 |
| NO990124L (no) | 1999-03-11 |
| JP2000514445A (ja) | 2000-10-31 |
| WO1998002438A1 (en) | 1998-01-22 |
| CZ8999A3 (cs) | 1999-06-16 |
| NO990124D0 (no) | 1999-01-12 |
| AP9901434A0 (en) | 1999-03-31 |
| AU3443997A (en) | 1998-02-09 |
| EA199900022A1 (ru) | 1999-08-26 |
| EP0912570B1 (en) | 2003-09-10 |
| TR199900049T2 (xx) | 1999-04-21 |
| DE69724789T2 (de) | 2004-07-01 |
| ATE249458T1 (de) | 2003-09-15 |
| ES2206729T3 (es) | 2004-05-16 |
| CA2260061A1 (en) | 1998-01-22 |
| BR9710359A (pt) | 1999-08-17 |
| US6174889B1 (en) | 2001-01-16 |
| HRP970371A2 (en) | 1998-08-31 |
| ID19403A (id) | 1998-07-09 |
| PL331221A1 (en) | 1999-07-05 |
| EP1304110A2 (en) | 2003-04-23 |
| EP0912570A1 (en) | 1999-05-06 |
| US6723726B1 (en) | 2004-04-20 |
| PE91198A1 (es) | 1999-01-15 |
| YU1099A (en) | 1999-11-22 |
| DE69724789D1 (de) | 2003-10-16 |
| EP1304110A3 (en) | 2003-12-17 |
| CN1230187A (zh) | 1999-09-29 |
| IS4939A (is) | 1998-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6723726B1 (en) | Protein tyrosine kinase inhibitors | |
| US6391874B1 (en) | Fused heterocyclic compounds as protein tyrosine kinase inhibitors | |
| US6207669B1 (en) | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors | |
| US10654832B2 (en) | 3-(benzoimidazol-2-YL)-indazole inhibitors of the Wnt signaling pathway and therapeutic uses thereof | |
| US10202377B2 (en) | 3-(1H-benzo[D]imidazol-2-yl)-1H-pyrazolo[3,4-C]pyridine and therapeutic uses thereof | |
| KR102010611B1 (ko) | 인다졸-3-카르복사미드 및 WNT/β-카테닌 신호생성 경로 저해제들로써의 이들 용도 | |
| US10463651B2 (en) | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-indazoles and therapeutic uses thereof | |
| JP4102185B2 (ja) | キナゾリンジトシル酸塩化合物 | |
| JPH11508906A (ja) | 複素環式化合物およびそれらを含む医薬組成物 | |
| US20110160185A9 (en) | Pyrrolopyrimidine derivatives as jak3 inhibitors | |
| WO1997013771A1 (en) | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors | |
| MXPA99000483A (en) | Biciclic heteroaromatic compounds as protein inhibitors tirosin cin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 19990113 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |